The use of minoxidil for hair loss has an important history. It was first used during the 1970 as an oral medication for refractory cases of high blood pressure. The molecule is a piperidinopyrimidine derivative, with the chemical structure 2,6-diamino- 4-piperidinopyrimidine 1-oxide .

It serves as an arteriolar vasodilator, acting specifically to open potassium channels. It also was found to have a side effect of hypertrichosis. , it was found to cause unwanted hair growth in 24% to 100% of patients. Hypertrichosis was also noted in 5 out of 6 patients treated with minoxidil. hypertrichosis is observed in a high frequency and at lower doses in women than in men No endocrine abnormalities have been associated, but darkening of the skin and the coarsening of facial features have been reported from long-term oral use.

Hypertrichosis caused by minoxidil was not
reported in the dermatology literature until 1979 That same year, the oral tablet form, Loniten
(Pharmacia & Upjohn, Bridgewater, NJ), was approved
by the FDA for hypertension. Other dermatologists
quickly took note in considering it for use in
treating different forms of hair loss. Zapacosta noted a reversal of androgenetic alopecia (AGA) in
a patient receiving oral minoxidil. However, there
were limitations to using the oral formulation, because
it could cause an unsafe drop in blood
pressure. Patients also experienced side effects of
severe water retention and weight gain, often
requiring concomitant treatment with a diuretic.

Therefore, several researchers tested its use as a
topical formulation for hair loss. Two controlled
trials using 1% topical minoxidil for alopecia areata
(AA) demonstrated cosmetically acceptable regrowth
in approximately half of patients. In
1984, topical minoxidil was used for the treatment
of AGA. Five patients with AGA and 10 with AA were
randomized to 1% or 5% topical minoxidil or placebo. Regrowth was seen in the 3 patients with
AGA who were given the 5% solution, suggesting a clinical dose response. Blood levels of minoxidil
were 0.5, 2.0, and 4.5 ng/mL 2 hours after application
to the scalp. None of the patients with AA regrew
hair, despite comparable blood levels.